SBIR Phase I: Determine Performance Characteristics During Cultivation of Living Organisms in a Novel Single-Use Horizontal Modular and Pressurizable Microbial Fermentor

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I project is to significantly improve the ability to generate biological pharmaceuticals. The biopharmaceutical industry is working to grow specific genetically engineered microbial cells that will produce a vaccine, injectable protein, or other products. There is a pressing need to culture unique microbes, starting from small scale batches, that rapidly scale to commercially viable batch sizes with high product output. A pressurized horizontal fermentor supports the industry’s drive towards single-use bags for microbial fermentation, as single-use fermentors lower operating costs and reduce cross-contamination that can result in loss of an entire batch. This scalable, single-use fermentor should achieve higher yields and allow drug producers to produce kilogram quantities of protein in a more cost-effective manner. This innovative, flexible, pressurizable, horizontal modular design will decrease time-to-market for vaccines, therapeutic proteins or other microbially manufactured products, from both small and large biologics producers, to combat global infectious, and other diseases, at reduced operating costs, saving lives. The proposed project will advance the knowledge of how microbial cells are cultivated in a horizontal, pressurized single-use bag fermentor. The knowledge gained will validate microbial production using a modular design that provides flexibility to adjust the capacity of the system, without significant facility modifications or cost. An initial prototype demonstrated highly encouraging results regarding fast mixing times, proper scalable power input, and excellent oxygen mass transfer. The design to be refined here has the potential to transform the biologics manufacturing industry by impacting the ability to generate high cell densities and reduce the cost of microbial manufacturing. Research objectives are to demonstrate: a fully developed design with the heat removal capacity required of high cell density fermentation (currently unachievable using existing industry vertical single-use fermentor designs); a pressurized bag system that can achieve oxygen transfer rates needed for high density cultures; and a scalable format that allows for rapid scaling to 3000 liters. A fully functioning test fermentor will be built and evaluated using both computational fluid dynamics analysis and laboratory testing of culture conditions. Experimental work will evaluate high agitation impellers, high gas flows, gas sparger designs, and system structural elements. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.